CMV infections following allogeneic BMT: risk factors, early treatment and correlation with transplant related mortality

Abstract

Background: The impact of early detection of CMV infections in allogeneic bone marrow transplantation (BMT) and of early treatment with ganciclovir is still uncertain.

Methods: 98 patients undergoing allogeneic BMT for hematologic malignancies (n = 91) or aplastic anemia (n = 7) were monitored weekly for the expression of the lower matrix protein pp65 of cytomegalovirus (CMV) on peripheral blood cells (PB) and urine sediments (U) as detected by C10 and C11 monoclonal antibodies (Clonab, Biotest) and immunoperoxidase. Bronchoalveolar lavage (BAL) cytospin preparations were also studied in patients with clinically documented interstitial pneumonia. Patients were considered to be infected with CMV if pp65 was detected in PB (n = 15) or BAL cells (n = 6), or in the presence of serum CMV-IgM with (n = 7) or without (n = 3) pp65-positive cells in urine sediments.

Results: The overall actuarial risk at 300 days of developing a CMV infection was 35%. CMV serum/status (IgG) pre-BMT of donor and/or recipient predicted the occurrence of CMV infections post-BMT: in neg/neg donor/recipient pairs (n = 17) the actuarial risk at 300 days was 0%, compared to 41% in pairs in which donor and/or recipient were CMV seropositive (n = 81) (p = 0.001). 24/31 patients were treated with ganciclovir (DHPG), and 17 survive. Mortality of patients treated early with DHPG on the basis of CMV antigenemia was 18% compared to 42% for untreated patients (p = 0.9). Pretransplant donor/recipient seropositivity accurately predicted transplant related mortality (TBM): 6% in neg/neg pairs vs 41% in all other combinations (p = 0.008).

Conclusions: The risk of developing CMV infections post-BMT can be predicted by pre-transplant serostatus, diagnosed by monitoring the expression of pp65-protein and correlates with transplant related mortality. The latter appears to be reduced by early treatment with DHPG.